Extracellular vesicles mirror the beneficial effect of wild olive (acebuche) oil in hypertensive‐like retinal pigment epithelial cells

Abstract

Aims/Purpose: Arterial hypertension (AH) leads to oxidative and inflammatory imbalance triggering hypertensive organ damage via different pathways. Oil extracted from the wild olive tree (acebuche, ACE) has previously shown antioxidant and anti‐inflammatory properties against hypertensive ocular damage when regularly consumed in the diet1,2. We therefore speculate that circulating extracellular vesicles (EVs) isolated from ACE oil‐fed animals might play a role in modulating pathological mechanisms surrounding AH‐related ocular diseases, including oxidative stress, migration and angiogenesis processes.Methods: Retinal pigment epithelium (ARPE‐19) cells mimicking a hypertensive phenotype induced by incubation with angiotensin II (AngII) were treated with EVs obtained from mice fed ACE oil or a reference extra virgin olive oil (EVOO). The 2′,7′dichlorodihydrofluorescein diacetate (DCFHDA) assay was used to estimate intracellular levels of reactive oxygen species (ROS). Furthermore, kinetic parameters for L‐arginine (L‐Arg) transport and the expression of L‐Arg transporter (CAT‐1) were also analysed. The wound‐healing assay was used to determine the anti‐migratory properties of ACE oil‐derived EVs, and the ability of EVs to modulate angiogenesis was assessed in aortic rings.Results: Both ACE oil‐ and EVOO‐related EVs were able to reduce ROS production in ARPE‐19 cells. The normalization of intracellular redox status by EVs might be exerted through modulation of L‐Arg uptake and CAT‐1 expression. Anti‐migratory and anti‐angiogenesis properties were also displayed by oil‐derived EVs, suggesting their potential benefit in the setting of neovascular ocular diseases.Conclusions: This is the first report to highlight the retinoprotective effects of EVs isolated from the plasma of animals subjected to ACE oil‐ and EVOO‐enriched diets against pathological events related to ocular diseases.